Perelman School of Medicine at the University of Pennsylvania

Section for Biomedical Image Analysis (SBIA)

Sex Differences

Connection-wise statistical analysis, as well as analysis of regional and global network measures, demonstrated unique sex differences in brain connectivity during the course of development. In all supratentorial regions, males had greater within-hemispheric connectivity, as well as enhanced modularity and transitivity, whereas between-hemispheric connectivity and cross-module participation predominated in females. However, this effect was reversed in the cerebellar connections. Analysis of these changes developmentally demonstrated differences in trajectory between males and females mainly in adolescence and in adulthood. Overall, the results suggest that male brains are structured to facilitate connectivity between perception and coordinated action, whereas female brains are designed to facilitate communication between analytical and intuitive processing modes.

While the presence of sex differences in human behavior is well documented, our knowledge of their anatomical foundations in the brain is still relatively limited. Our results suggest that behavioural sex differences, which indicate complementary of males and females, are accompanied by related differences in brain structure across development. When using subnetworks that are defined over functional and behavioral domains, we observed increased structural connectivity related to the motor, sensory and executive function subnetworks in males. In females, subnetworks associated with social motivation, attention and memory tasks had higher connectivity. Males showed higher modularity compared to females, with females having higher inter-modular connectivity. Applying multivariate analysis, we showed an increasing separation between males and females in the course of development, not only in behavioral patterns but also in brain structure. We also showed that these behavioral and structural patterns correlate with each other, establishing a reliable link between brain and behavior.


  1. Madhura Ingalhalikar, Alex Smith, Drew Parker, Theodore D. Satterthwaite, Mark A. Elliot, Kosha Ruparel, Hakon Hakonarson, Raquel E. Gur, Ruben C. Gur, Ragini Verma, "Sex differences in the structural connectome of the human brain", PNAS, 111(2), 823-828,
  2. Birkan Tunç, Berkan Solmaz, Drew Parker, Theodore D. Satterthwaite, Mark A. Elliott, Monica E. Calkins, Kosha Ruparel, Raquel E. Gur, Ruben C. Gur, Ragini Verma, "Establishing a link between sex-related differences in the structural connectome and behaviour", Phil. Trans. R. Soc. B 371(1688). pii: 20150111, February 2016,